A Study to Test Whether BI 706321 Combined With Ustekinumab Helps People With Crohn's Disease

Inclusion Criteria:

• Diagnosis of Crohn Disease (CD) for at least 3 months prior to visit 1, as confirmedat any time in the past by endoscopy and/OR, radiology, and supported by histology.

• Elevated C-reactive protein (≥ 5 mg/L) OR elevated fecal calprotectin (≥ 250 µg/g)

• Symptomatic CD defined as Crohn's Disease Activity Index (CDAI) ≥150.

• Presence of mucosal ulcers in at least one segment of the ileum or colon and aSimple Endoscopic Score for Crohn's disease (SES-CD) score ≥ 7 (for patients withisolated ileitis ≥4).

• Patients who are experienced at least 1 tumor necrosis factor (TNF) antagonists at adose approved for CD. Patients may have stopped TNF antagonist treatment due toprimary or secondary non-responsiveness, intolerance, or for other reasons.

• May be receiving a therapeutic dose of the following:

• Oral 5-aminosalicylic acid (5-ASA) compounds must have been at a stable dosefor at least 4 weeks prior to randomisation and must continue on this doseuntil week 12 and/or

• Oral corticosteroids if indicated for treatment of CD must be at a prednisoneequivalent dose of ≤ 20 mg/day, or ≤ 9 mg/day of budesonide, and have been at astable dose for at least 2 weeks immediately prior to randomisation and mustcontinue on this dose until week 12. and/or

• Azathioprine (AZA), mercaptopurine (MP), or methotrexate (MTX), provided thatdose has been stable for the 8 weeks immediately prior to randomisation andmust continue on this dose until week 12.

• Women of childbearing potential must be ready and able to use highly effectivemethods of birth control.

• Further inclusion criteria apply

Exclusion Criteria:

• Have any current or prior abscesses, unless they have been drained and treated atleast 6 weeks prior to randomisation and are not anticipated to require surgery.Patients with active fistulas may be included if there is no anticipation of a needfor surgery and there are currently no abscesses present based on investigator'sjudgement.

• Have complications of CD such as strictures, stenosis, short bowel syndrome, or anyother manifestation that might require surgery, or could preclude the use ofSES-CD/CDAI to assess response to therapy, or would possibly confound the evaluationof benefit from treatment with BI 706321 (based on investigator's judgement).

• Patient with an inflammatory bowel disease (IBD) diagnosis other than CD.

• Have had any kind of bowel resection or diversion within 4 months or any otherintra-abdominal surgery within 3 months prior to visit 1. Patients with currentileostomy, colostomy, or ileorectal anastomosis are excluded.

• Treatment with:

• Any non-biologic medication for IBD (e.g.tacrolimus or mycophenolate mofetil,systemic corticosteroids), other than those allowed per inclusion criteria,within 30 days prior to randomisation

• Any biologic treatment with a TNF-alpha antagonist (adalimumab, infliximab,golimumab, certolizumab pegol) or vedolizumab (or a biosimilar of these drugs)within 4 weeks prior to randomisation. (If drug level testing for previouslyused biologic treatment confirms no detectable drug level before randomisation,patient can be enrolled despite not having completed 4 week from lasttreatment.)

• Any previous treatment with ustekinumab (or a biosimilar of this drug)

• Any previous treatment with an investigational (or subsequently approved)non-biologic/biologic drug for CD (including but not limited to JAK inhibitors [e.g. upadacitinib], S1P modulators, IL-23 inhibitors [e.g. risankizumab],antiintegrins).

• Any investigational drug for an indication other than CD during the course ofthe actual study and within 30 days or 5 half-lives (whichever is longer) priorto randomisation.

• Any prior exposure to rituximab within 1 year prior to randomisation.

• Positive stool examination for C difficile or other intestinal pathogens <30 daysprior to randomization

• Evidence of colonic moderate/severe mucosal dysplasia or colonic adenomas, unlessproperly removed

• Increased risk of infectious complications (e.g. recent pyogenic infection, anycongenital or acquired immunodeficiency (e.g. human immunodeficiency virus (HIV)),past organ or stem cell transplantation (with exception of a corneal transplant > 12weeks prior to screening) or have ever received stem cell therapy (e.g., Prochymal).Prior treatment with a somatic cell therapy product (e.g., Alofisel) is notexcluded, provided it was administered > 8 weeks prior to randomisation.

• Live or attenuated vaccination within 4 weeks prior to randomisation.

• Presence of clinically significant acute or chronic infections not otherwise listed,including viral hepatitis, COVID-19, or others based on investigator's judgement.

• A marked baseline prolongation of QT/QTc interval (such as QTcF intervals that aregreater than 450 ms for men, 470 ms for female) or any other relevantelectrocardiogram (ECG) finding at screening. Both have to be confirmed by repeatedECG recording.

• Further exclusion criteria apply